The overall goals of the Opella Component of the Program Project are to develop generally applicable NMR methods for determining the structures and describing the dynamics of membrane proteins, and to apply these methods to Vpu in membrane environments. The availability of uniformly isotopically labeled Vpu in the model membranes of micelles, bicelles, and bilayers enables multidimensional solution NMR and solid-state NMR experiments to be utilized for determining the structure and describing the dynamics of Vpu over a wide range of timescales. The NMR studies are an integral part of the broadly based approach to describing the structural and function of Vpu presented in this proposal, which includes all of the major experimental and theoretical methods available for the characterization of proteins. The results will be directly applied in the development of drugs to interfere with the functions of Vpu and the virus lifecycle as we seek effective treatments for AIDS.